Aromatic Substitution Reactions Chapter 17 Aromatic Substitution Reactions OrgChem-Chap17

17.1 Mechanism for Electricphilic Aromatic Substitution Organic Chemistry II Fall 1999 17.1 Mechanism for Electricphilic Aromatic Substitution Arenium ion resonance stabilization OrgChem-Chap17 Chapter 18

Example 1. Example 2. OrgChem-Chap17

Example 2. Mechanism of the nitration of benzene OrgChem-Chap17

Addition reaction vs. Electrophilic aromatic substitution OrgChem-Chap17

Stability Ga < Gs Bezene is very stable so it is very diificult to break the resonance stabilization OrgChem-Chap17

Is the addition reaction possible for a benzene ? Very difficult because of the stability of the product resonance stabilization OrgChem-Chap17

17.2 Effect of Substituent Why ? Resonance stabilization 17 times faster than the substitution of benzene Why ? Resonance stabilization OrgChem-Chap17

Ortho attack Meta attack Para attack Meta and para attack is favored CH3 is an ortho/para directing group OrgChem-Chap17

Nitration of anisole (methoxy benzene) 10,000 times faster than the substitution of benzene Why ? Resonance stabilization OrgChem-Chap17

The effect of methoxy group Inductive effect, then as the oxygen is electronegative Methoxy is deactivating group not true 2. Resonance effect explanation is possible This is what scientists are doing, you also should have this attitude, then find reasons. Otherwise no result at all. Therefore, any group that has an unshared pair of electrons is the ortho/para director OrgChem-Chap17

Nitration of nitrobenzene 1. 1017 times slower than the substitution of benzene 2. meta director OrgChem-Chap17

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Activating group (elecron donating group): ortho/para director Until now, Activating group (elecron donating group): ortho/para director Deactivationg group (elecron withdrawing group): meta dircectot Exception: Halogens, ortho/para derector + deactivating group 1. 17 times slower than the substitution of benzene 2. ortho/para director OrgChem-Chap17

F is highly electronegative, therefore inductive withdrawing effect is stronger than the resonance effect Cl, Br, and I are not very electronegative, while the resonance effect is not strong enough as the methoxy Because the overlapping netween 2p AO of carbon and 3p(Cl), 4p(Br), 5p(I) AOs are not good. (2p AO for oxygen) Still halogens are ortho/para director because there is the resonance effect although it is much weaker. Nose ring theory ! Accurate experiment results are most important ! OrgChem-Chap17

Two ortho positions and one para position, therefore statistically the ratio or ortho to para products should be 2 to 1, Which is generally true! (nitration of toluene) Steric effect ! OrgChem-Chap17

See P 680 OrgChem-Chap17

17.3 Effect of Multiple Substituent Methyl group controls the regiochemistry, because methyl group is a strong activating group Rule: Groups that are closer to the top of Table 17.1 controls the regiochemistry! OrgChem-Chap17

17.4 Nitration OrgChem-Chap17

Preparation of NO2+ OrgChem-Chap17

A problem occurs with amino substitution N with unpaired electrons looks like a activating group and o/p director. But under acidic condition it can be protonated, then deactivating group and m director. Although the amine (strong activating group) conc. is very low, 18% is para product! OrgChem-Chap17

Amide group: much less basis, still activator and o/p director Example, OrgChem-Chap17

17.5 Halogenation Mechanism Same as the nitration Resonance stabiliztion, Activating group faciliate the reaction + AlCl3 + HCl OrgChem-Chap17

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17.6 Sulfonation Fuming sulfuric acid OrgChem-Chap17

Mechanism OrgChem-Chap17

17.7 Friedel-Craft Alkylation OrgChem-Chap17

Mechanism of the Friedel-Craft Alkylation OrgChem-Chap17

Drawbacks The alkyl groups that is added to the ring is an activated group: a large amount of products w/ two or more alkyl groups Aromatic compound w/ strongly deactivating groups cannot be alkylated. Rearrangement Because OrgChem-Chap17

Other ways to generate carbocations Strong acid, TsOH, can eliminate water, then CH3-ph-CH2+ can be generated Other examples Lewis acid is used OrgChem-Chap17

Synthetic detergents OrgChem-Chap17

BHT and BHA are anti oxidant added to food prepared by Friedel-Crafts alkylation reactions OrgChem-Chap17

17.8 Friedel-Craft Acylation Generation of acyl cation OrgChem-Chap17

Drawback: like the alkylation, this reaction does not work with strongly deactivated substrates (m directors) Examples OrgChem-Chap17

Examples OrgChem-Chap17

17.9 Electrophilic Substitution of Polycyclic Aromatic Compounds Why the 1 position is preferred? OrgChem-Chap17

Containing stable benzene ring OrgChem-Chap17

17.10 Nucleophilic Aromatic Substitution; Diazonium ion OrgChem-Chap17

Examples OrgChem-Chap17

17.11 Nucleophilic Aromatic Substitution; Addition-Elimination OrgChem-Chap17

Not SN2 but Addition-Elimination Mechanism Not SN2 but Addition-Elimination OrgChem-Chap17

The order of leaving group ability Examples OrgChem-Chap17

17.12 Nucleophilic Aromati Substitution; Elimination-Addition When there is no electron withdrawing group at o/p position, then elimination-addition occurs with very strong base (amide anion) or with weak base at high temperature OrgChem-Chap17

Mechanism OrgChem-Chap17

Benzyne The existence of benzyne OrgChem-Chap17

17.13 Some Additional Useful Reactions Reduction of nitro group to amine using hydrogen and a catalyst or by using acid and a metal (Fe, Sn, or SnCl2) Application OrgChem-Chap17

Reduction of carbonyl group (aldehyde or ketone) to a methylene group 1. Clemmenson reduction 2. Wolff-Kishner reduction 3. Catalytic hydrogenation OrgChem-Chap17

H2/Pt reduction vs Wolff-Kishner and Clemmenson reduction H2/Pt works for the carbonyl attached to the aromatic ring Wolff-Kishner and Clemmenson reduction do not have this restriction Oxidation of alkyl groups bonded to the aromatic ring If the carbon bonded to the ring is not tertiary OrgChem-Chap17

17.14 Synthesis of Aromatic Compound OrgChem-Chap17

Preparation of m-chlorobenzene and p-chlorobenzene Preparation of o-bromophenol OrgChem-Chap17

Preparation of m-bromochlorobenzene Problem: both chloro and bromo groups are o/p directors Solution: use NO2, a m director Preparation of m-bromotoluene Problem: methyl group is an o/p director Solution: use NO2, the m director OrgChem-Chap17

Preparation of m-butylbenzenesulfonic acid Benzene sulfonic acid cannot be alkylated because the Friedel-Craft alkyl- or acylation does not work with deactivating group OrgChem-Chap17

Preparation of OrgChem-Chap17 bezene